Previously we have shown that patients with primary biliary cirrhosis (PBC) have abnormal regulatory function of T cells. To study further whether abnormalities of lymphocyte function in PBC are due to altered function of T cell subpopulations, phenotypic and functional characteristics of CD4+ T cells were examined. The proportion of CD4+ T cells expressing the Leu-8 and CD45R antigens was normal in patients with PBC. The capacity of CD4+, lEU-8- T cells to provide helper function for PWM-stimulated immunoglobulin synthesis by B cells in vitro was similar in patients and controls. However, in contrast to normal individuals and patients with other liver diseases, CD4+, Leu-8+ T cells from patients with PBC did not suppress immunoglobulin synthesis. Whereas treatment of CD4+ T cells from normal individuals with anti-Leu-8 monoclonal antibody enhanced their suppressor function, similar treatment of CD4+ T cells from patients with PBC did not increase their suppressor function. To determine whether the abnormal regulatory function of CD4+, Leu-8+ T cells was due to a defect of cell activation, the response of CD4+ T cell subpopulations to mitogenic stimulation was examined. The proliferative responses of CD4+, Leu-8- T cells from patients with PBC and controls were similar, but the proliferative responses of CD4+, Leu-8+ T cells from patients with PBC were lower than those of control cells. Since the CD4+, Leu-8+ T cell population plays a role in suppressing immunoglobulin synthesis and is contained within the autoreactive T cell population, the abnormal function of this T cell subpopulation in patients with PBC may play a central role in defective immunoregulation found in this disease.